Publications by authors named "Reza Hajiaghaee"

38 Publications

Efficacy and safety of Sophora alopecuroides var. alopecuroides seed extract for opioid detoxification: A randomized, double-blind, and placebo-controlled clinical trial.

Phytother Res 2020 May 3;34(5):1108-1113. Epub 2019 Dec 3.

Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The seeds of Sophora alopecuroides L. var. alopecuroides (S. alopecuroides) have alleviated morphine withdrawal in mice. Therefore, in this study, the alkaloid composition of S. alopecuroides extract was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analysis. Moreover, 50 abstinent opium addicts consumed three 400 mg extract capsules once daily and 50 other patients took placebo for 8 days. At the baseline and days 3 and 8, the clinical opiate withdrawal scale (COWS) was used to assess withdrawal symptoms. At the baseline and Day 8, the patients' blood levels of serum glutamate oxaloacetate transferase; serum glutamate pyruvate transferase; alkaline phosphatase; total, direct, and indirect bilirubins; creatinine and blood urea nitrogen; complete blood count; and prothrombine time were measured. The groups' parameter values were also compared. Sophocarpine, matrine, and sophoramine were the major alkaloids constituting, respectively, 32.85, 26.55, and 6.91% of the extract. The extract decreased the COWS score at Days 3 and 8 significantly compared with the placebo (p < .001). The extract did not significantly affect the blood parameters' values compared with the placebo (p > .05). There was no adverse drug effect. In conclusion, the extract reduces the acute opioid withdrawal symptoms and seems to have good safety and tolerability.
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http://dx.doi.org/10.1002/ptr.6578DOI Listing
May 2020

Process optimisation for green synthesis of zero-valent iron nanoparticles using .

IET Nanobiotechnol 2019 Apr;13(2):160-169

Essential Oil Research Institute, University of Kashan, Kashan, Iran.

The potential of in the iron nanoparticles (FeNPs) production was evaluated for the first time. The influences of the variables such as incubation time, temperature, and volume ratio of the extract to metal ions on the nanoparticle size were investigated using central composite design. The appearance of SPR bands at 284 nm in UV-Vis spectra of the mixtures verified the nanoparticle formation. Incubating the aqueous extract and metal precursor with 1.5 volume ratio at 50°C for 30 min leads to the formation of the smallest nanoparticles with the narrowest size distribution. At the optimal condition, the nanoparticles were found to be within the range of 35-50 nm. Experimental measurements of the average nanoparticle size were fitted well to the polynomial model satisfactory with of 0.9078. Among all model terms, the linear term of temperature, the quadratic terms of temperature, and mixing volume ratio have the significant effects on the nanoparticle average size. FeNPs produced at the optimal condition were characterised by transmission electron microscopy, thermogravimetry analysis (TGA), and Fourier-transform infrared spectroscopy. The observed weight loss in the TGA curve confirms the encapsulation of FeNPs by the biomolecules of the extract which were dissociated by heat.
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http://dx.doi.org/10.1049/iet-nbt.2018.5040DOI Listing
April 2019

Effects of standardized hydro-alcoholic extract of leaf on hypertension and biochemical parameters in hypertensive hyperlipidemic type 2 diabetic patients: a randomized, double-blind and placebo-controlled clinical trial.

Avicenna J Phytomed 2019 Jan-Feb;9(1):44-53

Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.

Objective: To study the blood pressure, lipid and glycemic effects and safety of leaf in the hypertensive hyperlipidemic type 2 diabetic patients.

Materials And Methods: The patients took 350 mg standardized plant leaf hydro-alcoholic extract capsule (n=50) or placebo capsule (n=50) three times daily alongside conventional drugs for 2 months. At the baseline and endpoint, systolic and diastolic blood pressures and blood levels of fasting glucose (FG), 2-hr postprandial glucose (2hPPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), LDL-C, triglyceride, HDL-C, SGOT, SGPT and creatinine were determined in both groups. To evaluate the extract safety, serum SGOT, SGPT and creatinine levels were tested; also, the patients were requested to report any adverse effects.

Results: FG, 2hPPG, HbA1c, TC, LDL-C, triglyceride and systolic and diastolic blood pressures were decreased, whereas HDL-C was increased significantly in the extract group compared to those of the placebo group at the endpoint (for all cases, p<0.05). The extract did not significantly influence other parameters and no adverse effects were reported.

Conclusion: leaf hydro-alcoholic extract as an adjunct to the conventional drugs has additional antihypertensive as well as anti-dyslipidemic and anti-hyperglycemic effects in hypertensive hyperlipidemic type 2 diabetic patients. Besides, the extract lacks hepatic, renal and patient-reported adverse effects.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369317PMC
February 2019

Anticancer potential of Ferula hezarlalehzarica Y. Ajani fraction in Raji lymphoma cell line: induction of apoptosis, cell cycle arrest, and changes in mitochondrial membrane potential.

Daru 2018 Dec 9;26(2):143-154. Epub 2018 Nov 9.

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, 71348-45794, Iran.

Background: Cancer is a major cause of mortality. The present study evaluates the antitumor effects of Ferula hezarlalehzarica Y. Ajani fractions on various cancer cell lines, including the Raji Burkitt's lymphoma cells.

Methods: We evaluated the cytotoxic activity of various fractions of F. hezarlalehzarica against tumor cell lines by the MTT assay. Annexin V-PE/7-AAD and cell cycle analysis were assessed by flow cytometry. Expressions of genes associated with cell death and proliferation (Bax, Bcl-2, Fas, and c-Myc) were determined using real-time PCR. Alteration in mitochondrial membrane potential (MMP) was examined by JC-1 dye staining.

Results: The hexane fraction of F. hezarlalehzarica showed the highest degree of cytotoxicity against Raji cells (IC = 31.6 μg/ml). Flow cytometry analysis showed that 200 μg/ml of the fraction induced apoptosis in >96% of Raji cells after 24 h. In cell cycle analysis, at the same concentration, the percentage of apoptotic cells in the sub G1phase increased to 95.25 ± 1.76% at 48 h of treatment. The fraction induced cell cycle arrestat the G0/G1phase. Exposure to 100 μg/ml of the fraction after 48 h increased the percentage of G0/G1 cells (76.3 ± 6.08%) compared to the negative control (<50%). Treatment with75μg/ml of fraction reduced the expressions of Bcl-2 (0.23 ± 0.008-fold) and c-Myc (0.68 ± 0.07-fold) and increased Bax (1.75 ± 0.31-fold) and Fas (5.02 ± 0.74-fold; p < 0.01). We observed a decrease in MMP (≈0.4, p < 0.05) at ≥100 μg/ml and this effect remained almost unchanged until 48 h.

Conclusions: The F. hezarlalehzarica hexane fraction induced apoptosis in Raji cells by changing the expression of apoptosis-related genes, cell cycle distribution, and MMP. These data suggested a potential effectiveness of F. hezarlalehzarica for inducing cell death in lymphoma cells. Graphical abstract ᅟ.
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http://dx.doi.org/10.1007/s40199-018-0219-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279669PMC
December 2018

Bio-guided fractionation and isolation of active component from Tragopogon graminifolius based on its wound healing property.

J Ethnopharmacol 2018 Nov 8;226:48-55. Epub 2018 Aug 8.

Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Ethnopharmacological Relevance: Tragopogon graminifolius (T. graminifolius) from Asteraceae family has been used as a remedy in Persian traditional medicine for the treatment of various disorders such as wound healing.

Aim Of The Study: The purpose of this study is to investigate the compounds of T. graminifolius, which are responsible for its wound healing activity.

Materials And Methods: The experiment was performed in three phases; each phase consisted of fractionation of extracts followed by scratch assay. The results of the scratch assay were expressed using scratch closure index (SCI), representing the contraction of scratch.

Results: In phase I, Ethyl acetate fraction (E) showed the maximum SCI (61.7 ± 3.5) that was selected for more fractionation in the next phase. In phase II, 12 fractions were obtained and labeled as fractions E- A to L, respectively. Based on the SCI of fractions, EF (SCI=68.9 ± 0.6) was the most active fraction in phase II and selected for further fractionation in phase III. In phase III, 8 fractions were resulted by fractionation of EF and labeled as EF- 1-8. Fraction EF5 with the highest SCI (30.8 ± 3.0) was the most effective fraction and Luteolin was the main component. Luteolin significantly improved viability of fibroblast cells and increased cell population that was accompanied by decreased cell apoptosis. Luteolin-induced cell number increase in the S and G2M phases of the cell cycle, further confirms the proliferative effect of this compound.

Conclusion: The results showed that the total extract and fractions of T. graminifolius stimulate proliferation and migration of skin fibroblast cells and Luteolin is one of the active compounds responsible for these effects.
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http://dx.doi.org/10.1016/j.jep.2018.08.002DOI Listing
November 2018

Gas Chromatography, GC/Mass Analysis and Bioactivity of Essential Oil from Aerial Parts of : Antimicrobial, Antioxidant, AChE Inhibitory, General Toxicity, MTT Assay and Larvicidal Activities.

J Arthropod Borne Dis 2017 Sep 8;11(3):414-426. Epub 2017 Sep 8.

Department of Pharmacognosy, Faculty of Pharmacy and Medicinal Plant Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: We aimed to investigate different biological properties of aerial parts essential oil of Boiss and larvicidal activity of its volatile oils from all parts of plant.

Methods: Essential oil was prepared by steam distillation and analyzed by Gas chromatography and GC/Mass. Antioxidant, antimicrobial, cytotoxic effects and AChE inhibitory of the oil were investigated using DPPH, disk diffusion method, MTT assay and Ellman methods. Larvicidal activity of essential oil against malaria vector was carried out according to the method described by WHO.

Results: In GC and GC/MS analysis, 58 compounds were identified in the aerial parts essential oil, of which E-verbenol (9.66%), isobutyl acetate (25.73%) and E-β-caryophyllene (8.68%) were main compounds. The oil showed (IC= 111.2μg/ml) in DPPH and IC= 21.5 mg/ml in the investigation of AChE inhibitory. Furthermore, the oil demonstrated toxicity with (LD= 1.1μg/ml) in brine shrimp lethality test and with (IC= 22.0, 25.0 and 42.55 μg/ml) on three cancerous cell lines (MCF-7, A-549 and HT-29) respectively. LC of stem, root, aerial parts, fruits, and flowers essential oils against larvae of were equal with 10.46, 22.27, 20.50, 31.93 and 79.87ppm respectively. In antimicrobial activities, essential oil was effective on all specimens except , and

Conclusion: The essential oil showed moderate antioxidant activity, strong antimicrobial properties and good toxic effect in brine shrimp test and MTT assay on three cancerous cell lines.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758637PMC
September 2017

Evaluating the effect of Myrtus communis on programmed cell death in hydatid cyst protoscolices.

Asian Pac J Trop Med 2017 Nov 28;10(11):1072-1076. Epub 2017 Oct 28.

Department of Social Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Objective: To evaluate the possible involvement of programmed cell death strategy in hydatid cyst protoscolices following treatment with Myrtus communis (M. communis) as an herbal medicine.

Methods: Protoscolices were aseptically collected from sheep liver hydatid cysts. Evaluating the effect of M. communis extract on programmed cell death and increased activity of caspases 3, 8, and 9 in hydatid cyst protoscolices was conducted by treating the protoscolices with different concentration (5, 50, and 100 mg/mL) of M. communis extract at 37 °C and 5% CO for 4 h by using the Bradford test and ELISA commercial kits.

Results: The extract of M. communis at all concentrations led to initiation of programmed cell death in protoscolices and this effect, was only significant at 50 and 100 mg/mL concentrations, compared to the negative control (P < 0.05). Also, the activity of caspases 3, 8, and 9 in hydatid cyst protoscolices, was shown that the extract at all 3 concentrations could only increase the activity of caspases 3 and 9. Moreover, a significant increase in the activity of caspase 3 was only observed at concentrations 50 and 100 mg/mL by 37.00% and 66.19% while a significant increase in the activity of caspase 9 at the same concentrations was observed by 20.89% and 63.67%, respectively (P < 0.05).

Conclusions: The extract of M. communis at different concentrations could increase the activity of caspases 3 and 9 and caused programmed cell death in hydatid cyst protoscolices however, this effect was significant at high concentrations of the extract.
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http://dx.doi.org/10.1016/j.apjtm.2017.10.010DOI Listing
November 2017

Protoscolicidal and immunomodulatory activity of Ziziphora tenuior extract and its fractions.

Asian Pac J Trop Med 2016 11 22;9(11):1062-1068. Epub 2016 Oct 22.

Department of Social Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Objective: To evaluate the scolicidal and immunomodulatory effect of the Ziziphora tenuior (Z. tenuior) extract and its fractions.

Methods: Protoscolices were treated with six concentrations (3, 5, 10, 25, 50, and 100 mg/mL) of Z. tenuior extract and its fractions (ethanol, petroleum ether, ethyl acetate and chloroform) in periods of 10, 20, 30, 40, 50 and 60 min, and viability of protoscolices was evaluated using the 1.0% eosin. To examine the immunomodulatory effects of Ziziphora and its fractions on macrophage cells, the non-toxic concentration of extract and different fractions determined by MTT assay, and the Griess reaction was used to measure the level of nitrite as an indicator of nitric oxide by the macrophage cells in 10, 100 and 200 μg/mL in 24 h at 37 °C.

Results: In this study, the Z. tenuior extract at 10 mg/mL concentration was able to kill all protoscolices during 20 min. By increasing the concentration to 25 mg/mL, the scolicidal time reduced to 10 min. Regarding the effect of different fractions of Z. tenuior, the ethanolic fraction showed the highest scolicidal activity. The extract demonstrated an inhibitory effect on the activity of macrophages and reduced nitric oxide production. Although the petroleum ether and ethanolic fractions of the extract reduced nitric oxide production, nevertheless, this effect was only significant at 10 and 100 μg/mL concentrations (P < 0.05).

Conclusion: The Z. tenuior extract and its fractions were effective against protoscolices yet the effect of total extract was considerable. Our findings indicates that the extract and its ethanolic and petroleum ether fractions could have anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.apjtm.2016.09.008DOI Listing
November 2016

In vitro protoscolicidal effects of various concentrations of Ziziphora tenuior L. extract at different exposure times.

Avicenna J Phytomed 2016 Jul-Aug;6(4):376-82

Department of Social Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Objective: Hydatidosis is one of the most important zoonotic diseases and surgery is still the main treatment for this problem. One of the side effects of hydatid cyst surgery is recurrence, thus, searching and assessment of some new agents such as medicinal plant extracts are very important. In the present study, the scolicidal effect of ethanolic extract of Ziziphora tenuior (Z. tenuior) was investigated.

Materials And Methods: Protoscolices were aseptically collected from sheep livers containing hydatid cyst and used in the experiments. Z. tenuior extract was used at concentration of 3-100 mg/ml for 10-60 min. Viability of protoscolices was determined by 0.1% eosin staining.

Results: Based on our results, Z. tenuior extract at concentration of 10 mg/ml killed all protoscolices after 20 min. However, this medicinal plant at concentration of 25 mg/ml destroyed all protoscolices in a shorter exposure time (10 min). Therefore, the scolicidal activity of the extract at 10 and 25 mg/ml concentrations was considerably effective in lower concentrations and shorter exposure times.

Conclusion: The findings of this study showed that the ethanolic extract of Z. tenuior produces high scolicidal activity; it may be used as an appropriate and effective scolicidal agent in hydatidosis surgery. This is the first report on the protoscolicidal activity of Z. tenuior.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967833PMC
August 2016

Hydroalcoholic extract of Myrtus communis can alter anxiety and sleep parameters: a behavioural and EEG sleep pattern study in mice and rats.

Pharm Biol 2016 Oct 29;54(10):2141-8. Epub 2016 Mar 29.

a Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR , Karaj , Iran ;

Context: Myrtus communis L. (Myrtaceae), myrtle, is an evergreen shrub with strong antibacterial, anti-inflammatory, antihyperglycemic and antioxidant activities. Also, it is used as a sedative-hypnotic plant in Iranian traditional medicine.

Objective: This study evaluates the effect of 80% ethanolic extract of M. communis leaves on sleep and anxiety in mice and rats.

Materials And Methods: Male NMRI mice were subjected to open field, righting reflex, grip strength and pentylentetrazole-induced seizure tests. Male Wistar rats were used to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep. They were treated with 25-400 mg/kg doses of the extract intraperitoneally.

Results: The applied doses (50-200 mg/kg) of M. communis extract increased vertical (ED50 = 40.2 ± 6.6 mg/kg) and vertical and horizontal activity (ED50 = 251 ± 55 mg/kg), while treatment with 200 and 400 mg/kg attenuated muscle tone significantly compared to vehicle treated animals (p < 0.001 for all) in a dose-independent manner. Also, a significant hypnotic and not anticonvulsant effect was observed when animals were treated with 200 mg/kg of the extract (p < 0.01). In this regard, electroencephalography results showed that REM sleep time was decreased (2.4 ± 0.5%), while total and NREM sleep times were increased significantly compared to the control group of mice (82.5 ± 7.6%).

Discussion And Conclusion: The data show the anxiolytic and muscle relaxant effect of the extract without anticonvulsant activities. The anxiolytic, myorelaxant and hypnotic effects without effect on seizure threshold are in line with the effect of a alpha 2 GABA receptor agonist.
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http://dx.doi.org/10.3109/13880209.2016.1148175DOI Listing
October 2016

In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells.

BMC Complement Altern Med 2016 Mar 15;16:101. Epub 2016 Mar 15.

Department of Exercise Science, Sports Centre, University Malaya, 50603, Kuala Lumpur, Malaysia.

Background: Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments.

Methods: Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined.

Results: The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells.

Conclusions: Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.
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http://dx.doi.org/10.1186/s12906-016-1064-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791772PMC
March 2016

Apoptosis Cell Death Effect of Scrophularia Variegata on Breast Cancer Cells via Mitochondrial Intrinsic Pathway.

Adv Pharm Bull 2015 Sep 19;5(3):443-6. Epub 2015 Sep 19.

Physiology Department, Qazvin University of Medical Sciences, Qazvin, Iran.

Purpose: Scrophularia variegata M. Beib. (Scrophulariaceae) is an Iranian medicinal plant which is used for various inflammatory disorders in traditional medicine. In this study we evaluated the anti-cancer and cytotoxic effects of the Scrophularia variegata (S. variegata) ethanolic extract on the human breast cancer cell line.

Methods: The cytotoxicity effect of the extract on MCF-7 cells was evaluated by MTT assay. In addition, Caspase activity, DNA ladder and Cell death were evaluated by ELISA, gel electrophoresis and Annexin V-FITC/PI staining, respectively.

Results: The S. variegata extract showed significant effect cytotoxicity on MCF-7 human breast cancer cell line. Treatment with the extract induced apoptosis on the breast cancer cells by cell cycle arrest in G2/M phase. The results indicated that cytotoxicity activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation as well as an increase of the amount of caspase 3 and caspase 9. In addition, the phytochemical assay showed that the extract had antioxidant capacity and also flavonoids, phenolic compounds and phenyl propanoids were presented in the extract.

Conclusion: Our findings indicated that S. variegata extract induced apoptosis via mitochondrial intrinsic pathway on breast cancer by cell cycle arrest in G2/M phase and an increase of caspase 3 and caspase 9. However future studies are needed.
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http://dx.doi.org/10.15171/apb.2015.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616888PMC
September 2015

A Randomized Clinical Trial Study: Anti-Oxidant, Anti-hyperglycemic and Anti-Hyperlipidemic Effects of Olibanum Gum in Type 2 Diabetic Patients.

Iran J Pharm Res 2014 ;13(3):1003-9

School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Diabetes is a common metabolic disease in the world that has many adverse effects. Olibanum gum resin (from trees of the genus Boswellia) has traditionally been used in the treatment of various diseases such as diabetes. The aim of this study was the comparison of Olibanum gum resin effect with placebo on the treatment of type 2 diabetes. Inclusion criteria was diabetic patients with fasting blood sugar (FBS) =140-200 mg/dL. This study has been designed as double-blined clinical trial on 71 patients with type 2 diabetes and the patients randomly were divided to interventional and placebo groups. The patients on standard anti-diabetic therapy (metformin) treated with Olibanum gum resin (400 mg caps) and placebo tow times per day for 12 weeks, respectively. At the end of the twelfth week, the FBS, HbA1c, Insulin, total Cholesterol (Chol), LDL, Triglyceride (TG), HDL and other parameters were measured. The Olibanum gum resin lowered the FBS, HbA1c, Insulin, Chol, LDL and TG levels significantly (p < 0.001, p < 0.001, p <0.001, p = 0.003, p < 0.001 and p < 0.001, respectively) without any significant effects on the other blood lipid levels and liver/kidney function tests (p > 0.05) compared with the placebo at the endpoint. Moreover, this plant showed anti-oxidant effect and also no adverse effects were reported. The results suggest that Olibanum gum resin could be used as a safe anti-oxidant, anti-hyperglycemic and anti-hyperlipidemic agent for type 2 diabetic patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177622PMC
October 2014

Immunomodulatory effects of Ziziphora tenuior L. extract on the dendritic cells.

Daru 2014 Sep 17;22:63. Epub 2014 Sep 17.

Background: Ziziphora tenuior L. (Kakuti in Persian) is used in traditional medicine for treatment of gastrointestinal disorders as carminative and analgesic plant. The other usages of this plant are included treatment of diarrhea and nausea. Therefore in the present study we evaluated the immunomodulatory effects of the ethanolic extract of this plant on the dendritic cells (DCs).

Results: Ziziphora tenuior L. extract significantly (p = 0.002) increased the level of surface expression of CD40 as an important co-stimulatory marker on DCs compared to the control. However this extract did not change CD86 and MHC-II molecules, so it could promote DCs phenotypic maturation. Treatment of DCs with the extract resulted in slightly increased of the production of (IL-12); however, this change was not significant. In addition, the ability of treated DCs to stimulate allogenic T cells proliferation and cytokines secretion was examined in the co-cuture of these cells with T cells in mixed lymphocyte reaction (MLR). Z. tenuior L. at the 100 μg/ml concentration inhibited the proliferation of allogenic T cells and also significantly (P < 0.001) increased the level of IL-10. Moreover, the extract at 10-100 μg/ml concentration caused slightly increase in IFN-γ production and decreased IL-4 cytokines but these changes were not significant.

Conclusions: These findings indicated that Z. tenuior L. extract can modulate immune response by induction of CD40 expression on DCs and cytokine production; whereas it can inhibit T cell stimulating activity of DCs in high concentration. These findings possibly in part explain the traditional use of this plant in treatment of immune-mediated disorders. However future studies are needed.
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http://dx.doi.org/10.1186/s40199-014-0063-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172836PMC
September 2014

Two matrix metalloproteinase inhibitors from scrophularia striata boiss.

Iran J Pharm Res 2014 ;13(1):149-55

Pharmacognosy and Pharmaceutics Department of Medicinal plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.

Many species belonging to the Scrophularia genus have been used since ancient times as folk remedies for many medical conditions such as scrofulas, scabies, tumors, eczema, psoriasis, inflammations. The aim of this study was to characterize the matrix metalloproteinases (MMPs) inhibitor compounds of the Scrophularia striata extract by bio-guide fractionation. The aerial parts of S. striata were collected and different extracts were sequentially prepared with increasingly polar solvents. The MMPs inhibitory activity of the crude extract and its fractions were evaluated by the Zymoanalysis method. The pure compounds were purified from the active fraction by chromatography methods. Chemical structures were deduced by nuclear magnetic resonance and mass spectrometry. Two active compounds (acteoside and nepitrin) were identified by bio-guide fractionation. The inhibitory effects of nepitrin and acteoside at 20 µg/mL were about 56 and 18 percent, respectivly. The inhibitory effects of acteoside at 80 µg/mL were increased to about 73 percent. In summary, the results suggest that nepitrin effectively inhibited MMPs inhibitory activity at low concentrations, whereas acteoside showed inhibition at high concentrations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985265PMC
April 2014

Anti-aging effects of some selected Iranian folk medicinal herbs-biochemical evidences.

Iran J Basic Med Sci 2013 Nov;16(11):1170-80

Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Objective(s): In the current study, the effects of selected folk medicinal herbs were evaluated in D-galactose-induced aging in male mice.

Materials And Methods: Male BALB/c mice were randomly divided into 12 groups composing sham, control, and treated groups. Aging was induced by administration of D-galactose (500 mg/kg/day for 6 weeks). A positive control group was assigned that received vitamin E (200 mg/kg/day). The extract of herbs was prepared, lyophilized, and used in this study. The herbs were administered by gavage for 4 weeks to D-galactose-aged animals at the selected doses (mg/kg/day) as follows: Zingiber officinale (250), Glycyrrhiza glabra (150), Rosmarinus officinalis (300), Peganum harmala (50), Aloe vera (150), Satureja hortensis (200), Teucrium scordium (200), Hypericum perforatum (135) and Silybum marianum (150). One group of animals was assigned as sham and not given D-galactose.

Results: At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), NF-kappaB (NF-κb), total antioxidant power (TAP), thiobarbituric acid reactive substances (TBARS) as lipid peroxidation (LPO) marker and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood.

Conclusion: These data for the first time indicate significant anti-aging potential of examined herbs. RESULTS showed that D-galactose induces a significant oxidative stress and promotes proinflammatory cascade of aging while all herbs more or less recovered these changes. Among 9 herbal extracts, Silybum marianum showed the best effect in restoring aging changes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909629PMC
November 2013

Inhibitory and cytotoxic activities of salvia officinalis L. Extract on human lymphoma and leukemia cells by induction of apoptosis.

Adv Pharm Bull 2013 7;3(1):51-5. Epub 2013 Feb 7.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Purpose: Salvia officinalis L., also known as Maryam Goli, is one of the native plants used to Persian medicinal herbs. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized crude methanol extracts prepared from Salvia officinalis L., on a non-Hodgkin's B-cell lymphoma (Raji) and human leukemic monocyte lymphoma (U937), Human acute myelocytic leukemia (KG-1A) and Human Umbilical Vein Endothelial (HUVEC) cell lines.

Methods: The effect of methanolic extract on the inhibition of cell proliferation and cytotoxic activity was evaluated by Dye exclusion and Micro culture tetrazolium test (MTT) cytotoxicity assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determined whether the mechanism involves induction of apoptosis or necrosis.

Results: The present results demonstrated that methanolic extract at 50 to 800 μg/ml dose and time-dependently suppressed the proliferation of KG-1A, U937 and Raji cells by more than 80% (p<0.01), with ascending order of IC50 values in 24: KG-1A (214.377 μg/ml), U937 (229.312 μg/ml) and Raji (239.692 μg/ml) when compared with a chemotherapeutic anticancer drug, paclitaxel (Toxol), confirming the tumour-selective cytotoxicity. The crude extract however did not exert any significant cytotoxic effect on normal cell line HUVEC (IC50>800 Ag/ml). Nucleosome productions in KG-1A, Raji and U937 cells were significantly increased respectively upon the treatment of Salvia officinalis L. extract.

Conclusion: The Salvia officinalis L. extract was found dose and time-dependently inhibits the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.
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http://dx.doi.org/10.5681/apb.2013.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846054PMC
December 2013

Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial.

J Psychopharmacol 2014 Jul 15;28(7):677-85. Epub 2013 Oct 15.

Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran

The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms.
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http://dx.doi.org/10.1177/0269881113508830DOI Listing
July 2014

Antioxidant and neuroprotective effects of Scrophularia striata extract against oxidative stress-induced neurotoxicity.

Cell Mol Neurobiol 2013 Nov 3;33(8):1135-41. Epub 2013 Sep 3.

Department of Immunology, Qazvin University of Medical Sciences, Qazvin, Iran,

In this study, the neuroprotective effect of Scrophularia striata Boiss (Scrophulariaceae) extract, a plant growing in northeastern of Iran, against oxidative stress-induced neurocytotoxicity in PC12 was evaluated. The PC12 cell line pretreated with different concentrations (10, 50, 100, and 200 μg/ml) of the extract and then treated with H2O2 to induce oxidative stress and neurotoxicity. Survival of the cells, reactive oxygen species (ROS) generation, and apoptosis were measured using MTT assay, fluorescent probe 2',7'-dichlorofluorescein diacetate, and annexin V/propidium iodide, respectively. Moreover, the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) was used to evaluate the antioxidant capacity of the plant extract. Phytochemical assay by thin layer chromatography showed that the main components, including phenolic compounds, phenyl propanoids and flavonoids, were presented in the S. striata extract. The extract in concentrations of 50-200 μg/ml protected PC12 cells from H2O2-induced toxicity. The survival of the cells at concentration of 200 μg/ml was 64 % compared to that of H2O2 alone-treated cells (48 %) (p < 0.001). The extract also dose-dependently reduced intracellular ROS production (p < 0.001). Moreover, the extract showed antioxidative effects and decreased apoptotic cells. Collectively, these findings indicated the ability of S. striata to decrease ROS generation and cell apoptosis and also suggest the presence of the neuroprotective agents in this plant.
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http://dx.doi.org/10.1007/s10571-013-9979-7DOI Listing
November 2013

Aspirin for treatment of lithium-associated sexual dysfunction in men: randomized double-blind placebo-controlled study.

Bipolar Disord 2013 Sep 8;15(6):650-6. Epub 2013 Aug 8.

Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: The aim of the present study was to assess the effect of aspirin on lithium-related sexual dysfunction in men with stable bipolar affective disorder (BAD).

Methods: In a randomized, double-blind, placebo-controlled study, 32 men with stable BAD who had been on lithium maintenance therapy randomly received aspirin (240 mg/day) or placebo for six weeks. The International Index for Erectile Function (IIEF) was used to assess sexual symptoms at baseline, Week 3, and Week 6. Depressive and mania symptoms and plasma lithium concentrations were assessed at baseline and Week 6. Side effects were assessed using a checklist.

Results: Thirty patients (15/group) completed the study. Baseline and endpoint lithium concentrations and mania and depressive symptoms did not differ significantly between the two groups. Significant effects of time × treatment interaction were observed for total score [Greenhouse-Geisser: F(1.410,39.466) = 6.084, p = 0.010] and erectile function [Greenhouse-Geisser: F(1.629,45.602) = 7.250, p = 0.003]. By Week 6, patients in the aspirin group showed significantly greater improvement in the total (63.9% improvement from the baseline) and erectile function domain (85.4% improvement from the baseline) scores than the placebo group (14.4% and 19.7% improvement from the baseline, p-values = 0.002 and 0.001, respectively). By Week 6, 12 (80%) patients in the aspirin group and three (20%) patients in the placebo group met the criteria of minimal clinically important change [χ(2) (1) = 10.800, p = 0.001]. Other IIEF domains also showed significant improvement at the end of the trial. The frequency of side effects was similar between the two groups.

Conclusion: Aspirin effectively improves lithium-related sexual dysfunction in men with stable BAD.
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http://dx.doi.org/10.1111/bdi.12108DOI Listing
September 2013

Protective effects of Scrophularia striata in Ovalbumin-induced mice asthma model.

Daru 2013 Jul 9;21(1):56. Epub 2013 Jul 9.

Pharmacognosy & Pharmaceutics department of Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.

Background: Scrophularia striata Boiss. (Scrophulariaceae) is a plant growing in the northeastern part of Iran and being used as a traditional herb for various inflammatory disorders.This study was designed to investigate the protective effects of the Scrophularia striata extract in Ovalbumin (OVA) induced-asthma mice model.

Methods: OVA-sensitized mice were intrapritonealy treated with two doses (100 and 200 mg/kg) of the extract on days 8 to 14 separately. Broncoalveolar lavage fluids (BALF) was collected 48 h after the final OVA challenge and then the number of eosinophils and other inflammatory cells were assessed by direct microscopic counting. In addition, total immunoglubolin (Ig) E and OVA-specific IgE levels in serum, IL-4 and IL-5 cytokines in BALF were determined by Enzyme-Linked Immunosorbent Assay. Moreover, phytochemical assay by thin layer chromatography (TLC) and the 2, 2 diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the main compounds and the antioxidant capacity of the plant extract, respectively.

Results: The results showed that the main components; including flavonoids, phenolic compounds and phenyl propanoids were presented in the S. striata extract. In addition, the treatment with extract significantly reduced the number of inflammatory cells and suppressed T-helper 2 (Th2) cytokines including IL-4 and IL-5 in BALF. Also, total IgE and OVA-specific IgE levels in the serum decreased.

Conclusion: Collectively, it is concluded that the extract has the potential to modulate the Th2 cytokines and could be used as immunomodulatory agent in the treatment of allergic asthma.
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http://dx.doi.org/10.1186/2008-2231-21-56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751247PMC
July 2013

Coumarin compounds of Biebersteinia multifida roots show potential anxiolytic effects in mice.

Daru 2013 Jun 27;21(1):51. Epub 2013 Jun 27.

Background: Traditional preparations of the root of Biebersteinia multifida DC (Geraniaceae), a native medicinal plant of Irano-Turanian floristic region, have been used for the treatment of phobias as anxiolytic herbal preparation.

Methods: We utilized the phobic behavior of mice in an elevated plus-maze as a model to evaluate the anxiolytic effect of the plant extract and bio-guided fractionation was applied to isolate the active compounds. Total root extract, alkaline and ether fraction were administered to mice at different doses 30 and 90 min prior to the maze test. Saline and diazepam were administered as negative and positive controls, respectively. The time spent in open and closed arms, an index of anxiety behavior and entry time, was measured as an index of animal activity.

Results: The total root extract exhibited anxiolytic effect which was comparable to diazepam but with longer duration. This sustained effect of the crude extract was sustained for 90 min and was even more after injection of 45 mg/kg while the effect of diazepam had been reduced by 90 min. The anxiolytic effect factor was only present in the alkaline fraction and displayed its effect at lower doses than diazepam while pure vasicinone as the previously known alkaloid did not shown anxiolytic effect. The effect of the alkaline fraction was in a dose dependent manner starting at 0.2 mg/kg with a maximum at 1.0 mg/kg. Bio-guided fractionation using a variety of chromatographic methods led to isolation and purification of three coumarin derivatives from the bioactive fraction, including umbelliferone, scopoletin, and ferulic acid.

Conclusion: For the first time, bio-guided fractionation of the root extract of B. multifida indicates significant sustained anxiolytic effects which led to isolation of three coumarin derivatives with well-known potent MAO inhibitory and anti-anxiety effects. These data contribute to evidence-based traditional use of B. multifida root for anxiety disorders.
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http://dx.doi.org/10.1186/2008-2231-21-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707806PMC
June 2013

Memantine add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized, double-blind, placebo-controlled study.

J Clin Psychopharmacol 2013 Jun;33(3):336-42

Department of Psychiatry, Kurdistan University of Medical Sciences, Sanandaj, Iran.

We aimed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia. In a double-blind placebo-controlled clinical trial, 40 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were stabilized on risperidone for a minimum of 8 weeks were randomized to either memantine (20 mg) or placebo in addition to risperidone, 6 mg/d, for eight weeks. Assessment was done using the Positive and Negative Syndrome Scale at baseline, week 4, and week 8. The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms, respectively. All 40 patients had at least one postbaseline measurement, and 38 patients completed the trial. Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point (P < 0.001). The same effect was observed for the total score (P < 0.001) and the general psychopathology subscale score (P = 0.002). There was no significant difference in reduction of positive symptoms score between the 2 groups (P = 0.757). Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups. Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia.
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http://dx.doi.org/10.1097/JCP.0b013e31828b50a7DOI Listing
June 2013

Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

J Psychiatr Res 2013 Apr 30;47(4):472-8. Epub 2013 Jan 30.

Razi Psychiatric Hospital, Welfare Sciences University, Iran.

Some 5-HT3 antagonists such as ondansetron have shown beneficial effects on negative symptoms of patients with schizophrenia. We aimed to evaluate the efficacy of granisetron (another 5-HT3 antagonist) add-on therapy in the treatment of negative symptoms of patients with stable schizophrenia. In a randomized, double-blind, and placebo-controlled study, forty stable patients with schizophrenia (DSM-IV-TR), were randomized to either granisetron (1 mg twice daily) or placebo (twice daily) in addition to risperidone up to 6 mg/day for eight weeks. The patients were assessed using positive and negative syndrome scale (PANSS) and extrapyramidal symptom rating scale (ESRS) at baseline, week 4 and 8. Hamilton depression rating scale (HDRS) was used to assess depression at baseline and week 8. Thirty-eight patients completed the trial. Granisetron group showed a significantly greater improvement on negative subscale than the placebo group at endpoint [t(38) = 6.046, mean difference (±95% CI) = 3.2(1.8-3.7), P < 0.001]. The same effect was observed for total score [t(38) = 4.168, mean difference (95% CI) = 3.2(1.6-4.7), P < 0.001]. However the placebo and granisetron groups did not differ in their reduction of positive and general psychopathology symptoms scores. HDRS scores and its changes did not differ between the two groups. The ESRS score at week 4 was significantly lower in the granisetron than the placebo group while the two groups showed similar ESRS score at week 8. Frequency of other side effects was similar between the two groups. In summary, granisetron add-on can safely and effectively reduce the primary negative symptoms of patients with schizophrenia.
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http://dx.doi.org/10.1016/j.jpsychires.2013.01.011DOI Listing
April 2013

Inhibition of Growth and Induction of Apoptosis in Fibrosarcoma Cell Lines by Echinophora platyloba DC: In Vitro Analysis.

Adv Pharmacol Sci 2013 14;2013:512931. Epub 2013 Jan 14.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Echinophora platyloba DC plant (Khousharizeh) is one of the indigenous medicinal plants which is used as a food seasoning and medicine in Iran. The objective of this study was to examine the in vitro cytotoxic activity and the mechanism of cell death of crude methanolic extracts prepared from Echinophora platyloba DC, on mouse fibrosarcoma cell line (WEHI-164). Cytotoxicity and viability of methanolic extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) assay. Our results demonstrated that the extract decreased cell viability, suppressed cell proliferation, and induced cell death in a time- and dose-dependent manner in WEHI-164 cells (IC50 = 196.673 ± 12.4 μg/mL) when compared with a chemotherapeutic anticancer drug, Toxol. Observation proved that apoptosis was the major mechanism of cell death. So the Echinophora platyloba DC extract was found to time- and dose-dependently inhibit the proliferation of fibrosarcoma cell possibly via an apoptosis-dependent pathway.
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http://dx.doi.org/10.1155/2013/512931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556855PMC
February 2013

Urease inhibitory activities of β-boswellic acid derivatives.

Daru 2013 Jan 2;21(1). Epub 2013 Jan 2.

Department of Medicinal Chemistry, Faculty of Pharmacy and Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Unlabelled:

Background And The Purpose Of The Study: Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative.

Methods: 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme.

Results: It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM).

Conclusion: The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage.
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http://dx.doi.org/10.1186/2008-2231-21-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575251PMC
January 2013

Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study.

Acta Med Iran 2012 ;50(11):723-8

Psychiatric Research Centre, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD) and -15.60±7.81 (mean±SD) for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD) and -22.40±9.90 (mean±SD) for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of buspirone was less effective than methylphenidate in the treatment of ADHD.
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July 2013

Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects.

Chin J Integr Med 2012 Dec 21. Epub 2012 Dec 21.

Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.

OBJECTIVE: To evaluate the beneficial effects of a mixture of Aloe vera (AV) and Matricaria recutita (German chamomile, GC) in an experimental model of irritable bowel syndrome (IBS). METHODS: IBS was induced by a 5-day restraint stress in rats including the groups of control (water), GC (300 mg/kg), loperamide (10 mg/kg), mixed AV and GC (50: 50 at doses of 150, 300 or 450 mg/kg assigned as Mix-150, Mix-300 and Mix-450, respectively) and the sham group which did not receive any restraint stress and was fed with saline. All medications were administered intragastrically by gavage for 7 days, 2 days as pre-treatment followed by 5 days during induction of IBS every day before restraining. RESULTS: The increased tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO) activity, and lipid peroxidation (LPO) in colonic cells in the control group were significantly decreased in the treatment groups. GC inhibited only small bowel transit while the AV/GC mixture delayed gastric emptying at the doses of 150 and 300 mg/kg. The AV/GC mixture also reduced colonic transit and small bowel transit at the dose of 150 mg/kg. CONCLUSIONS: The severity of stress-induced IBS was diminished by the AV/GC mixture at all doses used but not dose-dependently, via inhibiting colonic MPO activity and improving oxidative stress status. The effect of the mixture was more effective than GC alone. The present results support effectiveness of the AV and GC combination in IBS.
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http://dx.doi.org/10.1007/s11655-012-1027-9DOI Listing
December 2012

Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study.

J Psychiatr Res 2013 Feb 9;47(2):175-80. Epub 2012 Oct 9.

Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.

There is a growing body of evidence for the efficacy of memantine augmentation in patients with obsessive-compulsive disorder (OCD). However, to date, no double-blind study has addressed this issue. The objective of the present randomized double-blind placebo-controlled study was to evaluate efficacy and tolerability of memantine add-on treatment in patients with moderate to severe OCD. Forty-two patients with the diagnosis of OCD based on DSM-IV-TR who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of ≥21 were randomly assigned to memantine (10 mg/day for the first week, and 20 mg/day for the rest of the trial) or placebo in addition to fluvoxamine for eight weeks. Patients were assessed using Y-BOCS every two weeks. Thirty-eight patients completed the study. Repeated measure ANOVA showed significant effect for time × treatment interaction in total scale [F (2.096, 75.470) = 5.280, P = 0.006] and obsession [F (2.340, 94.547) = 5.716, P = 0.002] and near significant effect for compulsion subscales [F (2.005, 79.179) = 2.841, P = 0.065]. By week eight, all patients in the memantine group and six (32%) patients in the placebo group [P value of Fisher's exact test <0.001] met the criteria for partial and complete response. At the end of the trial, 17 (89%) patients in the memantine group compared with six (32%) patients in the placebo group achieved remission (χ(2)(1) = 13.328, P < 0.001). Frequency of side-effects was not significantly different between the two groups. In summary, we showed that memantine add-on to fluvoxamine significantly improved short-term outcomes in patients with moderate to severe OCD.
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http://dx.doi.org/10.1016/j.jpsychires.2012.09.015DOI Listing
February 2013

Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

Int J Neuropsychopharmacol 2013 May 24;16(4):783-9. Epub 2012 Sep 24.

Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.

Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).
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http://dx.doi.org/10.1017/S1461145712000880DOI Listing
May 2013